Major ovarian cancer clinical study announced using combination drug therapy

November 28, 2005

A clinical study of ovarian cancer initiated by investigators at Yale School of Medicine will combine the anti-cancer drug phenoxodiol with docetaxel for women with recurrent ovarian cancer.

“Advanced-stage ovarian cancer is one of the most devastating forms of cancer, with half of the women diagnosed with it dying within five years,” said principal investigator Thomas Rutherford, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale and a member of the Yale Cancer Center. “One of the imperatives facing doctors who treat these patients is to find ways to restore sensitivity to drugs such as taxanes once they start to lose that sensitivity.”

The Phase Ib/IIa clinical study is supported by Sanofi-Aventis and Marshall Edwards, Inc. It will combine phenoxodiol, which is in the investigational phase with docetaxel, a second-generation taxane–drug that inhibits cell growth by stopping cell division–commonly used in patients with recurrent or persistent ovarian cancer that has failed other therapies, including the first generation taxane paclitaxel. The clinical response rate to any chemotherapeutic is often limited due to rapid development of chemo-resistance in women with recurrent ovarian cancer.

The purpose of the study is to determine if the addition of phenoxodiol to docetaxel can improve clinical response and survival by delaying or preventing the development of chemo-resistance in women with recurrent ovarian cancer.

The study will enroll 60 women with recurrent epithelial ovarian, fallopian tube or abdominal cavity cancer after treatment with a platinum and paclitaxel. All 60 patients will be given docetaxel by injection weekly; half the patients will also be given oral phenoxodiol daily, and the other half a placebo tablet. Tumor response will be determined on the basis of tumor burden (RECIST criteria) in patients with measurable disease, and tumor marker levels (GCIG criteria) in patients with non-measurable disease. Disease free survival, the time from study enrollment to evidence of disease progression, will also be compared between the two groups. Treatment will continue for one year unless there is evidence of complete response, unacceptable toxicity or disease progression.

Rutherford said the rationale behind this study is based on two observations. The first is the demonstration in pre-clinical studies of the potent ability of phenoxodiol to

reverse chemo-resistance in human ovarian cancer cells to docetaxel, through the ablation of anti-apoptotic proteins in the tumor cells. The second is the encouragingly high tumor response rate observed in a current clinical study where phenoxodiol is being used to chemo-sensitize paclitaxel in advanced-stage ovarian cancer patients where the tumor is taxane-resistant or refractory.

“The highly encouraging pre-clinical and clinical data that we have seen with phenoxodiol when it has been used as a chemo-sensitizer to date, gives us optimism that this strategy will provide the means to improve the survival of these late-stage cancer patients,” Rutherford said.